Development of implantable MEMS for biomedical applications

Despite the advancements made in conventional drug delivery over the years, there are many difficulties in the application of conventional drug delivery in the management of chronic diseases. There is a current need for develop treatment methods which are targeted and controllable to overcome some of the difficulties associated with conventional drug delivery. Due to their unique properties, Microelectromechanical systems (MEMS) Technology applications in implantable drug delivery systems have many advantages and are showing great promise in disease treatment. A key advantage of MEMS drug delivery devices is their small size and controllability. This project features a small, implantable, controllable drug delivery device which leverages on the strengths of conventional drugs, while providing the targeted and controllable features which they are lacking. The proposed device has: i) large drug reservoir ( ~100 μl) to minimize refilling, ii) relatively small in size (13mm x 13 mm x 4 mm), iii) a low power 3 V electrode for long-term, controlled electrochemical actuation, iv) a long targeted drug delivery cannula with a backflow valve, v) high flow rate of 0.4 μl/s at 3 V and vi) highly biocompatible.Bachelor of Engineerin

Developing micro and nanostrategies for human cancer detection and therapy

In this thesis, micro and nano technologies were employed to create cancer therapies that can be customized for individuals by enhancing the therapeutic effects while simultaneously reducing the possible side-effects. Using a newly engineered Lab-On-a-Chip drug testing device, optimized drug formulations for killing the cancer in vitro were determined. These drug formulations were then loaded into multifunctional hybrid-polymeric nanoparticles for enhancing tumor uptake and improving providing targeted delivery in vivo. In addition, these nanoparticles were equipped with multimodal imaging capabilities (e.g. fluorescence and magnetic resonance imaging), allowing real-time monitoring of the biodistribution and efficacy of the nanodrugs in vivo. Lastly, to further improve the delivery of the nanodrugs locally, biocompatible microelectromechanical system devices were fabricated and implanted into small animals for evaluation of the pharmacokinetics of programmed drug delivery. The use of these approaches allows treatment to be tailored for the individual, thereby enhancing the therapeutic outcomes.Doctor of Philosophy (EEE

A sustainable approach to individualized disease treatment : The engineering of a multiple use MEMS drug delivery device

Individualized disease diagnosis and therapy has emerged as a new direction in the research of future medication. Over the past several years, innovative approaches based on microelectromechanical system (MEMS) technology have demonstrated promising potential in individualized therapy. In this contribution, a sustainable approach for the individualized treatment of chronic disease is presented using a compact, implantable and refillable MEMS drug delivery device with an electrolysis based actuator. As a demonstration, we utilized the device for programmable delivery of a chemotherapy drug for the treatment of pancreatic cancer with an in vitro configuration based on cancer cell colonies. After the delivery of drug using the device, the growth of the colonies has been greatly inhibited as compared with the control samples. These results show that our new approach has a great potential for future in vivo studies and opens up promising opportunities for future medication

Recent advances in radiation therapy and photodynamic therapy

10.1063/5.0060424APPLIED PHYSICS REVIEWS8

Synthesis and characterization of multifunctional hybrid-polymeric nanoparticles for drug delivery and multimodal imaging of cancer

In this study, multifunctional hybrid-polymeric nanoparticles were prepared for the treatment of cultured multicellular tumor spheroids (MCTS) of the PANC-1 and MIA PaCa-2 pancreatic carcinoma cell lines. To synthesize the hybrid-polymeric nanoparticles, the poly lactic-co-glycolic acid core of the particles was loaded with Rhodamine 6G dye and the chemotherapeutic agent, Paclitaxel, was incorporated into the outer phospholipid layer. The surface of the nanoparticles was coated with gadolinium chelates for magnetic resonance imaging applications. This engineered nanoparticle formulation was found to be suitable for use in guided imaging therapy. Specifically, we investigated the size-dependent therapeutic response and the uptake of nanoparticles that were 65 nm, 85 nm, and 110 nm in size in the MCTS of the two pancreatic cancer cell lines used. After 24 hours of treatment, the MCTS of both PANC-1 and MIA PaCa-2 cell lines showed an average increase in the uptake of 18.4% for both 65 nm and 85 nm nanoparticles and 24.8% for 110 nm nanoparticles. Furthermore, the studies on therapeutic effects showed that particle size had a slight influence on the overall effectiveness of the formulation. In the MCTS of the MIA PaCa-2 cell line, 65 nm nanoparticles were found to produce the greatest therapeutic effect, whereas 12.8% of cells were apoptotic of which 11.4% of cells were apoptotic for 85 nm nanoparticles and 9.79% for 110 nm nanoparticles. Finally, the study conducted in vivo revealed the importance of nanoparticle size selection for the effective delivery of drug formulations to the tumors. In agreement with our in vitro results, excellent uptake and retention were found in the tumors of MIA PaCa-2 tumor-bearing mice treated with 110 nm nanoparticles.MOE (Min. of Education, S’pore)Published versio

Standalone Lab-on-a-Chip Systems toward the Evaluation of Therapeutic Biomaterials in Individualized Disease Treatment

As each tumor is unique, treatments should be individualized in terms of their drug formulation and time dependent dosing. In vitro lab-on-a-chip (LOC) drug testing is a viable avenue to individualize treatments. A drug testing platform in the form of a customizable standalone LOC system is proposed for treatment individualization in vitro. The platform was used to individualize the treatment of pancreatic cancer by using PANC-1 and MIA PaCa-2 cell lines cultured on-chip. Using on-chip drug uptake, growth, and migration inhibition assays, the therapeutic effect of various treatment combinations was analyzed. Thereafter, optimized treatments were devised for each cell line. The individualized dosage for MIA PaCa-2 cell line was found to be between 0.05–0.1 μg/μL of doxorubicin (DOX), where the greatest growth and migration inhibition effects were observed. As the PANC-1 cell line showed resistance to DOX only formulations, a multidrug approach was used for individualized treatment. Compared to the DOX only formulations, the individualized treatment produced the same degree of migration inhibition but with 5–10 times lower concentration of DOX, potentially minimizing the side-effects of the treatment. Furthermore, the individualized treatment had an average of 672.4% higher rate of growth inhibition. Finally, a preliminary study showed how a tested formulation from the LOC system can be translated for use by employing a nanoparticle system for controlled delivery, producing similar therapeutic effects. The use of such systems in clinical practice could potentially revolutionize treatment formulation by maximizing the therapeutic effects of existing treatments while minimizing their potential side effects through individualization of treatment

Preparation of biofunctionalized quantum dots using microfluidic chips for bioimaging

Biofunctionalized quantum dots (QDs), especially protein-coated QDs, are known as useful targeted fluorescent labels for cellular and deep-tissue imaging. These nanoparticles can also serve as efficient energy donors in fluorescence resonance energy transfer (FRET) binding assays for multiplexed sensing of tumor markers. However, current preparation processes for protein-functionalized QDs are laborious and require multiple synthesis steps (e.g. preparing them in high temperature, making them dispersible in water, and functionalizing them with surface ligands) to obtain high quality and quantity of QD formulations. This significantly impedes the progress of employing QDs for clinical diagnostics use such as QDs-based immunohistofluorescence assay. Here, we demonstrate a one-step synthesis approach for preparing protein-functionalized QDs by using microfluidic (MF) chip setup. Using bovine serum albumin (BSA) molecules as the surface ligand model, we first studied and optimized the MF reaction synthesis parameters (e.g. reaction temperature, channel width and length) for making protein-functionalized QDs using COMSOL simulation modeling followed by experimental verification. Moreover, in comparison with the BSA-functionalized QDs synthesized from conventional bench-top method, BSA-QDs prepared using MF approach exhibit a much higher protein-functionalization efficiency, photostability and colloidal stability. The proposed one-step MF synthesis approach will provide a rapid, cost effective, and small-scale production of nanocrystals platform for developing new QD formulations in applications ranging from cell labeling to sensing of biomolecules. Most importantly, this approach will greatly reduce the chemical waste produced during the trial-and-error stage of developing and perfecting the desired physical and optical property of new QDs materials.Accepted versio

Amplified parallel antigen rapid test for point-of-care salivary detection of SARS-CoV-2 with improved sensitivity

10.1007/s00604-021-05113-4MICROCHIMICA ACTA189

RNase2 is a possible trigger of acute-on-chronic inflammation leading to mRNA vaccine-associated cardiac complication.

10.1016/j.medj.2023.04.001MedS2666-6340(23)00104-6